This project uses image processing techniques to analyze many types of biological, clinical and biomedical images. Current research includes the structural biology of macromolecules using electron micrograph imaging and 2D and 3D reconstructions, cataract image analysis, functional PET, MRI and functional MRI scans to analyze the relationship between anatomy and function as well as to develop better PET imaging systems, and ultrasound images of the heart to analyze blood flow. To answer important questions in structural biology, it is necessary to obtain high resolution 2D and 3D structural information about biological macromolecules. Biological specimens can be visualized in the electron microscope. At present we are continuing our efforts to investigate the structure of large animal viruses including human herpes simplex virus (type 1). In a related analysis of cytomegalovirus (CMV) new techniques have provided a structure that was previously unavailable. The computational demands of the 3-D reconstructions have prompted the use of DCRT's IBM SP2 Supercomputer. In addition, some of the steps in the 3D reconstruction of icosahedral virus capsids which are computationally slow are being farmed out to multiple processors in work-station clusters. Very high resolution 3D reconstructions of the bovine papillomavirus (bpv) capsid are being studied. This analysis, currently at 9A, leads the way to high resolution among all laboratories in the world. This result is being followed by a study of the papillomavirus capsid with bound antibodies. The purpose of these new analyses is to assist in the development of a vaccine. Bacteriophage T4, which is normally a prolate (elongated) icosahedral type virus has been produced using isometric mutants. Two forms of this viral capsid have been analyzed, and show, for the first time, the detailed structure of this class of bacteriophages. We are using similar 3-D reconstruction techniques to study the structure of L-A virus (from yeast) at higher resolution. This year, the analysis has been extended to 17A resolution, and has been accepted for publication. In another collaborative project we are providing structural information about variants and mutations of the poliovirus. Biomedical Image Processing also includes a number of clinical, biomedical, and laboratory support research efforts. Collaborative research with NEI has focused upon several areas. We have been developing a series of cataract images which could be utilized as standards for the physician to accurately grade cataracts. We are also developing a slit lamp which can be used by many sites for quantitative grading purposes. We have developed unique medical application software for use by the cardiology branch of the National Heart Lung and Blood Institute (NHLBI) which will contribute to the developing field of cardiac tissue viability studies. The software, in conjunction with an external calibration system developed by the FDA for ultrasound modulation testing, should prove to be the most accurate system yet designed to estimate myocardial tissue viability as a result of contrast agents reaching the coronary microcirculation. Our participation in the development of new animal PET scanner technology has extended image resolution far beyond what was available from previous state-of-the-art scanners. We have investigated the use of principal component analysis in the analyses of functional MRI images. An integral part of our image processing consulting is ongoing support for the NIH Image program (by Wayne Rasband). Our support includes continuing development of new algorithms and four supporting documents which are now distributed with the package.